The present invention relates to stable lithium amides and reagent compositions which are free of tetrahydrofuran and ethers. More particularly, the invention concerns the preparation of lithium amides and to reagent compositions thereof containing increased concentrations of the lithium amide in solution and capable of producing increased yields in subsequent reactions.
Lithium amides, for example, lithium diisopropopylamide are widely used as a reagents in the preparation of pharmaceuticals and specialty chemicals. Lithium amides are particularly useful for the preparation of lithium acetylide compounds which are used to form acetylenic substituted organic compounds such as steroid and fragrance intermediates. In order to form the lithium acetylide, acetylene is reacted with a lithium amide such as lithium diisopropylamide just prior to reacting the newly formed lithium acetylide with the ketone or other reagent in the same reactor. All of these steps are performed below 0.degree. C. Usually, it is necessary to add an ether cosolvent such as tetrahydrofuran at this point to increase the limited solubility of the reagents and the subsequently formed lithium salt of the product from the reaction with the ketone. The lithium amide may be added as a preformed solution or it may be formed in the same reactor by reacting an alkyllithium such as n-butyllithium with an amine such as diisopropyl amine. In either case the lithium amide usually exhibits lower solubility than desired for maximum reactivity and yet there is a need to minimize the amount of solvents employed.
In order to increase the concentration of the lithium amide in the preformed solutions, ethers such as tetrahydrofuran and or complexing agents such as organomagnesium compounds have been added to increase the solubility of the lithium amide in solution. The presence of the ethers makes these solutions unstable and they decompose on standing in storage. The presence of magnesium compounds in the reaction and subsequent workup is undesirable because the possibility of lower reactivity and yields of desired products plus the more difficult workup due to the presence of the formed magnesium oxide which is highly insoluble and formed during washing.
Additionally when tetrahydrofuran is used as the solvent it has been found necessary to limit the amount of tetrahydrofuran to no more than one mole for each mole of lithium amide in order to minimize degradation of the system.
Aromatic solvents were not utilized as the solvent for preparing preformed lithium amide solutions in the past because the increased solubility was not appreciated and the belief that there would result a degradation of the alkyl lithium in an aromatic solution.
U.S. Pat. No. 4,595,779 to Morrison et al relates to a composition and method for preparing lithium diisopropylamide by the reaction of lithium metal and diisopropylamine in tetrahydrofuran and an inert liquid hydrocarbon cosolvent including styrene as an electron carrier. However, the use of tetrahydrofuran is considered essential in the preparation when utilizing lithium metal.
The article of Keith Smith entitled "Lithiation and Organic Synthesis", Chemistry In Britain, January 1982, pages 29-32, discloses the preparation lithium dialkyl amides for use as lithiating agents by the reaction of organolithium reagents in aliphatic hydrocarbon solvents.
U.S. Pat. No. 3,542,512 to Honeycutt relates to the preparation of lithium amide by contacting lithium metal with liquid ammonia and then heating the mixture at a temperature above 150 degrees C. in an inert liquid medium. The inert liquid medium includes aromatic compounds having a boiling point above 200 degrees C.
It is an object of the present invention to provide a lithium amide reagent composition having greater amounts of the lithium amide in solution.
It is a further object of the invention to provide a process for preparing lithium amides in higher concentrations in solution and in a solvent which is stable.
It is a yet further object of the invention to solubilize lithium amides which are considered insoluble.
It is a yet still further object of the invention to prepare lithium amides in situ and to utilize the resulting mixture to carry on further reactions.
It is still another object of the invention to prepare novel lithium amides and reagent compositions thereof.